Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.

Journal Article (Clinical Trial;Journal Article;Multicenter Study)

OBJECTIVE: Glial cell line-derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). METHODS: Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15 microg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and (18)F-dopa uptake. RESULTS: At 6 months, mean percentage changes in "off" UPDRS motor score were -10.0% and -4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, -23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean (18)F-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension). INTERPRETATION: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased (18)F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome.

Full Text

Duke Authors

Cited Authors

  • Lang, AE; Gill, S; Patel, NK; Lozano, A; Nutt, JG; Penn, R; Brooks, DJ; Hotton, G; Moro, E; Heywood, P; Brodsky, MA; Burchiel, K; Kelly, P; Dalvi, A; Scott, B; Stacy, M; Turner, D; Wooten, VGF; Elias, WJ; Laws, ER; Dhawan, V; Stoessl, AJ; Matcham, J; Coffey, RJ; Traub, M

Published Date

  • March 2006

Published In

Volume / Issue

  • 59 / 3

Start / End Page

  • 459 - 466

PubMed ID

  • 16429411

International Standard Serial Number (ISSN)

  • 0364-5134

Digital Object Identifier (DOI)

  • 10.1002/ana.20737


  • eng

Conference Location

  • United States